Two cases of colon LST in transplanted liver patients.

Long-life immunosuppressive therapy increases the risk of de novo tumors in liver transplant recipients by decreasing the immune surveillance against malignant cells and oncogenic viruses. However, no cases of colon precancerous lesions have been reported in these subjects. Patient n. 1, a 73 yrs old male treated with calcineurin and purine synthesis inhibitors, showed at a per-protocol colono-scopy a 3 cm laterally spreading tumor (LST). Patient n. 2, a 73 yrs old male treated with calcineurin inhibitors, showed at a screening colonoscopy an LST occupying one third of the lumen circumference. Both subjects were asymptomatic, had been transplanted 14 years before, and in both cases, lesions showed severe dysplasia. LSTs represent 17.2% of advanced colorectal neoplasia (CRC) and risk factors are multifactorial. Immunosuppression may play a role which is however not completely understood. Based on this report, surveillance colonoscopy in liver transplanted patients should be considered.

A facebook survey to obtain alcohol-related information by young people and adolescents. An Italian study.

BACKGROUND: Alcohol consumption by adolescents and young adults is an issue of significant public concern. Internet-based Social Networking sites, such as Facebook, are potential avenues to reach young people easily. OBJECTIVE: to underline the innovation in proposing surveys to collect health-related information regarding young people alcohol consumption and other substances abuse by using Social Networking Websites, particularly Facebook. METHODS: A questionnaire investigating modalities of alcohol consumption, drinking patterns' risk behaviors and other substances abuse was proposed through a "Facebook event" to young Italian Facebook users aged between 16 and 32. Each Facebook user invited to the event was free to participate, to answer to the questionnaire and to invite his "Facebook friends". RESULTS: During the 89 days of permanence on the Social Network, 1846 Facebook users participated the event and 732 of them decided spontaneously to answer the questionnaire. The frequency of answering was 8.2 people per day. About 200 users wrote a positive comment to the initiative on the wall of the event. Sixty% of subjects participating the survey were females. Ninety-one% of people answering the questionnaire were alcohol consumers. More than 50% of alcohol consumers were also smokers. Approximately 50% of subjects were binge drinkers. Illegal drugs were used by the 22.2% of the interviewed people. CONCLUSIONS: Facebook resulted an efficient and rapid tool to reach young people from all over Italy and to propose surveys in order to investigate alcohol consumption and alcohol-related health problems in the youth.

Antioxidant enzymes in blood of patients with Friedreich's ataxia.

BACKGROUND AND AIMS: Increased generation of reactive oxygen species and mitochondrial dysfunction may underlie the pathophysiology of Friedreich's ataxia, the most common inherited ataxia, due to GAA expansion in a gene coding for a mitochondrial protein (frataxin), implicated in the regulation of iron metabolism. Because iron overload would cause oxidative stress in Friedreich's ataxia, we investigated the enzyme antioxidant system in the blood of 14 patients by determining superoxide dismutase, glutathione peroxidase, and glutathione transferase catalytic activities. We also studied the glutathione S-transferase genotype polymorphism in order to evaluate its possible influence on enzyme activity. METHODS: Blood samples were obtained from 14 unrelated patients with Friedreich's ataxia and 21 age matched healthy subjects. Antioxidant enzyme determinations were spectrophotometrically assayed using specific substrates; the glutathione S-transferase genotype polymorphism was analysed by endonuclease restriction mapping of exon 5 and 6 amplification products. RESULTS: There was a significant elevation of the superoxide dismutase/glutathione peroxidase activity ratio (0.037 (0.01) v 0.025 (0.008) of controls) and an 83% rise of glutathione transferase specific activity (0.22 (0.1) v 0.12 (0.03) nmol/min/mg protein) in blood of patients with Friedreich's ataxia than in the controls. The genotype polymorphism of glutathione S-transferase enzyme did not show any relevant differences when compared to that of healthy subjects. CONCLUSIONS: Data show an impairment in vivo of antioxidant enzymes in patients with Friedreich's ataxia and provide evidence of an increased sensitivity to oxidative stress, supporting a consistent role of free radical cytotoxicity in the pathophysiology of the disease.

Differential regulation of transcripts for dystrophin Isoforms, dystroglycan, and alpha3AChR subunit in mouse sympathetic ganglia following postganglionic nerve crush.

Previous data suggest that in mouse superior cervical ganglion (SCG) the dystrophin-dystroglycan complex may be involved in the axotomy-induced intraganglionic synapse remodeling. Here we analyzed the levels of mRNAs encoding dystrophins, dystroglycan (Dg), and the alpha3 subunit of the nicotinic acetylcholine receptor (alpha3AChR) in mouse SCG at various postaxotomy intervals. We found that axotomy downregulates the levels of transcripts for molecules related to synaptic transmission (alpha3AChR) and those presumably involved in postsynaptic apparatus organization (dystrophin isoforms) and upregulates the transcript encoding Dg, which, by binding dystrophin, bridges the actin cytoskeleton and several extracellular matrix proteins and may thus be involved in postaxotomy neuronal recovery. The observed transcriptional modulation of the components of dystrophin-dystroglycan complexes indicates their involvement in injury-induced neuronal plasticity and suggests a role in other forms of plasticity such as those required in learning and memory, functions often impaired in Duchenne muscular dystrophy patients.

[Experimental models of acute pancreatitis. Critical review]. / Modelli sperimentali di pancreatite acuta. Revisione critica.

Experimental models of acute pancreatitis have been developed for more than a century. Although not closely comparable to human disease, they have contributed to our understanding of the physiopathology and cell biology of the disease. The methods used for the induction are subjected to critical examination. In the relevant literature findings, the advantages of each group are underscored, and reference is made to their defects with regard to reproducibility and reliability, with a view to extending the results obtained to human pathology. A proper understanding and standardization of these models may enable us to choose the most suitable model for studying a given aspect of the disease or for evaluating new treatment protocols. The data collected has made it possible to select standardization criteria for a comparative experimental study in the laboratory.

[Instrumental innovation in suprapubic microcatheter]. / Innovación instrumental en microtalla suprapúbica.

In this work, we introduce a new instrument for placing suprapubic catheter which meet all the standard for this purpose that we take in consideration. We placed 36 suprapubic catheter in less time, made easy and without complication we suggest to use this instrument for better results.

Differential antagonism of amylin's metabolic and vascular actions with amylin receptor antagonists.

High affinity amylin binding sites are present in the rat nucleus accumbens. These sites bind [125I]amylin with an affinity of 27 pM and have high affinity for salmon calcitonin (sCT) and moderately high affinity for calcitonin gene related peptide (CGRP). N-terminally truncated peptides were tested for their ability to compete for [125I]amylin binding to these sites and to antagonize the metabolic and vascular actions of amylin. CGRP(8-37), sCT(8-32), and ac-[Asn30,Tyr32]sCT(8-32) (AC187) inhibited [125I]amylin binding to rat nucleus accumbens. Order of potency at inhibiting amylin binding (AC187 > sCT(8-32) > CGRP(8-37)) differed from the order of potency at inhibiting [125I]CGRP binding to SK-N-MC neuroblastoma cells (CGRP(8-37) > AC187 > sCT(8-32)) . AC187 was the most potent antagonist of amylin's effects on isolated rat soleus muscle glycogen metabolism, and it was more effective than either sCT(8-32) or CGRP(8-37) at reducing amylin-stimulated hyperlactemia in rats. In contrast, CGRP(8-37) was the most potent peptide at antagonizing amylin-induced hypotension in rats. Amylin's hypotensive actions appear to be mediated by a weak action at CGRP receptors, while its metabolic actions are mediated by receptors with a distinct antagonist profile. AC187 is a potent antagonist of amylin binding sites in nucleus accumbens and of amylin's metabolic actions.

Beta-structure in human amylin and two designer beta-peptides: CD and NMR spectroscopic comparisons suggest soluble beta-oligomers and the absence of significant populations of beta-strand dimers.

Intensity variation for the positive far UV CD band was observed for three 'beta-sheet' peptides. In 6% HFIP, an amyloidogenic species (human pancreatic amylin) displays, on standing, an extremely intense 192-nm band which diminishes upon physical agitation. A concurrently formed Tyr sidechain band at 274 nm disappears completely with agitation, linking the enhancement of the 192-nm band to the highly ordered stacking of beta-sheets. NMR studies indicate that the beta-states of the three peptides are oligomeric, not beta dimers. A membrane-forming EAK peptide displays NMR peaks due to the low concentration of 'random coil' monomers present in slow equilibrium with beta-oligomers; solutions of a more hydrophobic ELKA peptide, which displays an intense 195-nm band, contain only oligomeric species. NMR studies at 25% HFIP revealed the structural requirements for inhibition of beta-oligomer formation.

Selective amylin antagonist suppresses rise in plasma lactate after intravenous glucose in the rat. Evidence for a metabolic role of endogenous amylin.

Data presented here provide the first demonstration that circulating amylin regulates metabolism in vivo, and support an endocrine hormonal role that is distinct from its autocrine action at pancreatic islets. When rats were pre-treated with the potent amylin antagonist AC187 (n = 18), and then administered a 2 mmol glucose load, the rise in plasma lactate was less than in rats administered glucose only (n = 27; P < 0.02). When rats were treated so that plasma glucose and insulin profiles were similar (n = 8), the increase in plasma lactate in the presence of AC187 was only 50.3% as high as the increase when AC187 was absent (P < 0.001). These experimental results fit with the view that some of the lactate appearing in plasma after a glucose load comes from insulin-sensitive tissues. The experiments also support the view that an important fraction of the increase in lactate depends on processes inhibited by a selective amylin antagonist, most likely amylin action in muscle.

Molecular physiology of amylin.

Amylin is a 37-amino acid peptide first isolated, purified, and characterized from the amyloid deposits in the pancrease of type 2 diabetics. It is synthesized and secreted primarily from pancreatic beta cells along with insulin. The ability of amylin to potently reduce insulin-stimulated incorporation of glucose into glycogen in skeletal muscle requires both an intact 2Cys-7Cys disulfide bond and a COOH-terminal amide. Amylin has structural and functional relationships to two other messenger proteins, calcitonin and CGRP. Amylin has relatively potent calcitonin-like activity on bone metabolism and weaker CGRP-like activity on the vasculature. CGRP is a slightly weaker agonist than amylin for metabolic responses. Although rat calcitonins are weak, teleost fish calcitonins are very potent agonists for amylin's metabolic effects. This group of peptides appears to act on a family of related G protein-coupled receptors; several variant calcitonin receptors have recently been cloned and expressed. These receptors appear to be coupled to adenylyl cyclase in many instances; recent evidence supports the view that amylin's effects on skeletal muscle occur, at least in large part, through activation of the cAMP pathway.

Small peptide inhibitors of smooth muscle myosin light chain kinase.

The pentapeptide Ser-Asn-Val-Phe-Ala-OBzl has been identified as the smallest inhibitory peptide of myosin light chain kinase (MLCK) derived from the primary sequence of the light chain phosphorylation site. The specific contributions of individual amino acid side chains and backbone elements of this pentapeptide toward the stabilization of the enzyme-inhibitor (E-I) complex have been evaluated. The potency of these peptides as inhibitors of MLCK has been enhanced by the incorporation of synthetic nonnatural amino acids into the sequence. Finally, it has been demonstrated that these peptide sequences could be converted into pseudopeptides with synthetic nonpeptide subunits designed to mimic peptide bonds, and that certain pseudopeptides retained the high-affinity inhibition of the parent pentapeptides.

Action of gastrointestinal hormones on the myoelectric activity of the sphincter of Oddi in living rabbit.

The aim of this work was to compare the action of gastrointestinal (GI) hormones on the myoelectrical activity of the sphincter of Oddi. Using an experimental design previously described, we studied the electrical activity of the sphincter of Oddi and compared the percentage variation in the number of spikes before and after injection of hormones. Increasing doses of the following hormones were injected i.v. at random: CCK, OP-CCK, caerulein, bombesin, gastrin, secretin and glucagon. CCK and caerulein (as previously found), and also bombesin, OP-CCK and gastrin increased the spikes activity of the sphincter of Oddi. Secretin had no effect and glucagon decreased this activity. There was no tachyphylaxis, but a good dose-effect relationship for each hormone. Compared on a molar basis caerulein is 8 times more effective than CCK and OP-CCK which in turn are more potent than bombesin. Gastrin acts only at pharmacological doses.

[Treatment of hepatic metastases in tumors of the gastrointestinal tract. Considerations on 25 cases]. / Il trattamento delle metastasi epatiche nei tumori del tubo gastroenterico. Considerazioni su 25 casi.

Results with liver resection over a period of 3 yr in the treatment of metastases derived from tumours of the gastroenteric tube are reported. An account is given of the data and the techniques used by Italian and foreign workers for this purpose. A personal series of 25 cases is presented and its 2-yr survival figure is stated.

[Influence of cholestasis on enzymatic induction with phenobarbital and other enzymatic aspects: experimental studies on guinea pigs]. / Influenze della colostasi sul'induzione da fenobarbital e su altri aspetti enzimatici: osservazioni sperimentali sulla cavia

Investigations in guinea pigs to evaluate interferences between cholestasis and enzymatic induction by phenobarbital, and influences that both experimental conditions exert on the levels of gamma-glutamyl transpeptidase in microsomes and other subcellular fractions, have shown that: 1) cholestasis inhibits inductions of cytochrome P-450 from phenobarbital; 2) gamma-glutamyl transpeptidase is not an inducible enzyme in guinea pig; 3) rises or ferum gamma-glutanyl transpeptidase produced either by cholestasis or phenobarbital administration, are not related to an increased enzymatic synthesis in the various subcellular fractions of liver cell.